Fluorinated dialkali-alkaline earth pyrophosphates and method of producing same



United States Patent FLUORINATED DIALKALI-ALKALINE EARTH PYROPHOSPHATESAND METHOD OF PRO- DUCING SAME Henry V. Moss, Anniston, Ala., assignorto Monsanto Chemical Company, St. Louis, Mo., a corporation of DelawareNo Drawing. Application October 23, 1952, Serial No. 316,550

21 Claims. (Cl. 167-93) The present invention relates to a noveldentifrice base and to a method of preparing same.

An important object of the invention is to provide an improvedfluorinated polishing and cleansing agent for dentifrices.

Another object is to provide a dentifrice base in the form of a slightlysoluble complex fluorinated phosphate salt which provides an efiicientand reliable means for obtaining uniform distribution of the fluorinethroughout the dentifrice.

An additional object is to provide a fluorinated dentifrice base havingnone of the objectionable properties of prior dentifrices which containmechanical mixtures of alkaline earth salts and soluble or insolublefluorides.

A further object is to provide a dentifrice including the improvedfluorinated dentifrice base.

Other objects and advantages will be apparent to those skilled in theart as the description proceeds.

Most investigators of dental caries agree that this malady is caused bythe local disintegration of the tooth structure by the action ofbacteria upon food in the immediate environment of the tooth. As aresult of considerable research which followed the discovery that peopleliving in sections of the country where the drinking water containsfluorine in the proper concentrations suffer less from dental cariesthan those situated in localities where the drinking water is free orsubstantially free of fluorine, it is now generally accepted that thiselement is highly effective in the prevention and control of toothdecay.

It has been proposed to add soluble fluorides to the water supplies incaries susceptible areas, but this method of approach has a number ofdisadvantages.

One disadvantage of adding a soluble fluoride to drinking water is thatin the process of drinking only the anterior teeth come into contactwith the fluoride with the result that this compound has little, if any,beneficial effect on the other teeth. Another disadvantage is that inthe naturally. Other disadvantages of this method of treating andcontrolling dental caries are set forth in detail by Dr. Basil G. Bibbyin the Journal of the American Dental Association, vol. 31, No. 5, pages317-321 (March 1944).

It is also known that the external application of water solutions ofsoluble fluorides reduces the development of caries by rendering thetooth structure more resistant to attack and by reducing the prevalencein the saliva of Lucio-bacillus acidophilus which is recognized to beone of the important factors in inducing caries. Thus, rinsing the mouthafter meals with a dilute solution of sodium fluoride (5 parts permillion F) has been shown by Dr. "A. Paul Atkins to be a relativelysimple and effective way of applying this new knowledge (I. A. D. A.,vol. 31,

2 No. 5,353-357-March 1944). However, in order to carry through thisrelatively simple treatment, a solution of suitable strength must beprocured from a drugstore or other reliable source and a new habit mustbe formed of going through the additional chore of rinsing the mouthwith a special solution.

The basic concept of incorporating a fluoride in a dentifrice is notnovel as this is broadly disclosed in British Patent 3034/1914 to Lidgeyand U. S. Patent 1,943,856 to Cross. However, it will be apparent fromthe considerations which immediately follow that the compositionsdescribed in these patents do not provide a satisfactory means for thetreatment and prevention of dental caries.

First of all, the compounding of the dentifrices of the patents to Cross(1,943,856) and Lidgey (British 3034/ 1914) presents the difficulty ofuniformly distributing, by the usualmechanical means, the small amountof fluoride salt required. Further, even if it is assumed that ahomogeneous mixture could be obtained, there is danger of subsequentsegregation of the physically added fluoride which would result in anundesirable concentration of the fluoride in portions of the compoundeddentifrice while other portions would contain such a low concentrationof soluble fluoride as to aiford no protection against dental caries.

Moreover, dentifrice compositions such as disclosed in Patent 1,943,856to Cross, are excessively abrasive since bentonite'has a relativeabrasive index of 17, whereas the acceptable upper limit for dentifricebases should preferably not exceed 12. Therefore, such compositionswould be unacceptable today in the dentifrice art.

Furthermore, when soluble fluorides are incorporated in tooth pastessimilar to those disclosed by British Patent 3034/ 1914 to Lidgey and1,943,856 to Cross, they tend to react with the colloidal silica ofbentonite and/ or the alkaline earth compounds to form essentiallyinsoluble products. This renders the fluorine unavailable and at thesame time causes objectionable stiflening and caking of the tooth paste.

1 have discovered that the above disadvantages and difliculties can beovercome by providing acomposition of matter consisting essentially of adialkali-alkaline earth pyrophosphate containing about 1% to about 5% byweight of fluorine as an intimately and substantially uniformlydistributed component. This composition is prepared by reacting in anaqueous medium an alkaline earth salt such as an alkaline earthchloride, lactate, acetate and the like with a mixture of a solublefluoride and a tetra-alkali pyrophosphate. This results in theproduction of a slurry, which is filtered to separate the precipitatefrom the mothor liquor. This precipitate is then washed to remove thealkali salts corresponding to the acid radical of the alkaline earthsalt and dried. The product thus obtained is the dialkali-alkaline earthpyrophosphate containing various amounts of chemically combined fluorinedepending upon the amount of soluble fluoride initially employed.

In the preparation of fluorinated disodium calcium pyrophosphate, asoluble calcium salt such as calcium chloride, calcium lactate, calciumacetate, etc. is reacted, in the presence of an aqueous medium, with amixture of tetrasodium pyrophosphate and a soluble fluoride such assodium fluoride, potassium fluoride, ammonium fluoride, etc. Thereactants are employed in substantially the proportions required toproduce disodium calcium pyrophosphate containing about 1% to about 5%and preferably about 2% to about 3.5% by weight of fluorine. The initialcalcium salts are employed in the proportions ranging from theoreticalto substantially in excess of the theoretical requirements. For example,these saltsare employed in proportions ranging from about 0% to about 3200%, and preferably from about 10% to about 20% in excess of thatrequired to form disodium calcium pyro phosphate.

In a similar manner, by selecting the appropriate salts, fluorinateddisodium magnesium pyrophosphate, fluorinated dipotassium calciumpyrophosphate, fluorinated dipotassium magnesium pyrophosphate or thehydrates thereof may be prepared.

Production of fluorinated disodium calcium pyrophosphate tetraltydrate3.2 pounds of tetrasodium pyrophosphate was dissolved in three gallonsof water to form a solution containing between ten to fifteen percenttetrasodium pyrophosphate. To this solution 0.31 pound of sodiumfluoride was added. The solution of tetrasodium pyrophosphate and sodiumfluoride was heated with continuous stirring to 85 C., whereupon 1.34pounds of a twenty-five percent calcium chloride solution wasintroduced. This was about 10% in excess of the theoretical amount ofcalcium chloride necessary to produce disodium calcium pyrophosphate. Asthe calcium chloride was added, the precipitating so dium calciumpyrophosphate caused the mix to become very thick and viscous at onepoint in the mixing cycle,

but as the stirring was continued, the batch again thinned out and goodmixing resulted. The resulting slurry of fluorinated disodium calciumpyrophosphate tetrahydrate was heated at 85 C. to 95 C. for a period ofan hour, cooled to 50 C., filtered, washed to remove excess sodiumchloride and then dried at a temperature of 85 C.

The fluorinated disodium calcium pyrophosphate tetrahydrate produced bythe above-described process contained about 2.9% by weight of fluorine.This product was used in the treatment of the teeth of Syrian hamsters,and it was found to reduce the number of caries teeth by about 40%. Incontrast, thereto, samples of disodium calcium pyrophosphatetetrahydrate containing traces and about 0.4% of fluorine, respectively,had no effect in reducing the number of caries teeth.

The fluorinated dentifrice bases of the present invention may be used intooth pastes and tooth powders.

In the compounding of tooth pastes, I preferably employ about 40%-60% byweight of the dry base, which base may be combined with varyingpercentages of glycerine, gums, water, flavoring material, massingagents, etc. In addition there may be incorporated various wetting.emulsifying or foaming agents such as the esters of the higher aliphaticalcohols, for example, the water soluble salts of sulfuric acid estersof lauryl or myristyl alcohol. Or I may advantageously use in place ofthe latter, alkali metal salts, such as the sodium or potassium salts ofalkylated aromatic sulfonic acids, wherein the alkyl group contains from8 to 18 or more carbon atoms.

In the preparation of tooth powders I preferably employ the fluorinateddentifrice base in amounts varying from 90%99% by weight of the finalproduct, but a smaller proportion of the base may be used, if desired. Imay also incorporate other salts with the finely divided dentifricebase. In patricular, I may make mixtures of the fluorinated base withmagnesium pyrophosphate, dicalcium phosphate, tricalcium phosphate,calcium carbonate or insoluble sodium metaphosphate. I may alsoincorporate wetting, emulsifying or sudsing agents in dry form such asabove-mentioned.

Other types of wetting, emulsifying or sudsing agents which may beadvantageously added to tooth pastes and tooth powders containing myfluorinated dentifrice base are described in U. S. Patent No. 2,359,326to Moss et 31. Of these agents, those of the tasteless and odorlessvariety are particularly suitable for use in tooth powders.

The compositions embodying my invention, when used as dentifrice per seor in combination with other normal constituents in paste or powderedform, are capable of cleaning and polishing the teeth and of restoringand maintaining their natural lustre without abrading or scratching thesurface thereof. Moreover, they provide a novel and etlicient means foruniformly supplying controlled amounts of fluorine to the teeth.

Where the expression chemically combined fluorine" is used in thespecification and claims, it is to be understood that the fluorine ischemically combined with one or more of the elements of the composition.The exact nature of the chemical combination is not definitely known,but it is thought that the soluble fluoride is combined in such a manneras to either provide a slightly soluble complex-, mixedor double saltwith the dialkalialkaline earth pyrophosphate or an extremely intimatemixture of a fluoride with the dialkali-alkaline earth pyrophosphate. Inany event, the soluble fluoride is so intimately and uniformlyassociated with the dialkali-alkaline earth pyrophosphate as to providea unitary product which behaves essentially as a single compound.

The foregoing detailed description has been given for clearness ofunderstanding, and no unnecessary limitations should be understoodtherefrom, but the appended claims should be construed as broadly aspermissible in view of the prior art.

What I claim is:

l. The method, which comprises reacting together, in a liquid aqueousmedium, a mixture initially consisting essentially of an alkalifluoride, an alkali metal pyrophosphate and a soluble alkaline earthmetal salt to form a fluorinated alkali-alkaline earth metalpyorphospate, and recovering said fluorinated pyrophosphate, saidreactants being employed in the proportions required to yield adialkali-alkaline earth metal pyrophosphate containing about 1% to about5% by weight of chemically combined fluorine.

2. As a new composition of matter, a dialkali-alkaline earth metalpyrophosphate containing about 1% to about 5% by weight of chemicallycombined fluorine, said composition of matter being produced by themethod defined in claim 1.

3. The method, which comprises reacting together, in a liquid aqueousmedium, a mixture initially consisting essentially of an alkalifluoride, an alkali metal pyrophosphate and a soluble alkaline earthmetal salt to form a fluorinated alkali-alkaline earth metalpyrophosphate, and recovering said fluorinated pyrophosphate, saidreactants being employed in the proportions required to yield adialkali-alkaline earth metal pyrophosphate containing about 1% to about5% by weight of chemically combined fluorine, and said alkaline earthmetal being selected from the group consisting of calcium and magnesium.

4. As a new composition of matter, a dialkali-alkaline earth metalpyrophosphate containing about 1% to about 5% by Weight of chemicallycombined fluorine, said alkaline earth metal being selected from thegroup consisting of calcium and magnesium, said composition of matterbeing produced by the method defined in claim 3.

5. The method, which comprises reacting together, in a liquid aqueousmedium, a mixture initially consisting essentially of an alkalifluoride, an alkali metal pyrophosphate and a soluble alkaline earthmetal salt to form a fluorinated alkali-alkaline earth metalpyrophosphate, and recovering said fluorinated pyrophosphate, saidreactants being employed in the proportions required to yield adialkali-alkaline earth metal pyrophosphate containing about 2% to about3.5% by weight of chemically combined fluorine, and said alkaline earthmetal being selected from the group consisting of calcium and magnesium.

6. As a new composition of matter, an alkali-alkaline earth metalpyrophosphate containing from about 2% to about 3.5 by weight ofchemically combined fluorine, said alkaline earth metal being selectedfrom the group consisting of calcium and magnesium, said composition ofmatter being produced by the method defined in claim 5.

7. The method, which comprises reacting together, in a liquid aqueousmedium, a mixture initially consisting essentially of sodium fluoride,tetrasodium pyrophosphate and a water soluble calcium salt to form afluorinated disodium calcium pyrophosphate, and recovering saidfluorinated pyrophosphate, said reactants being employed in theproportions required to form disodium calcium pyrophosphate containingabout 1% to about 5% by weight of chemically combined fluorine.

8. As a new composition of matter, disodium calcium pyrophosphatecontaining about 1% to about 5% by weight of chemically combinedfluorine, said composition of matter being produced by the methoddefined in claim 7.

9. The method, which comprises reacting together, in a liquid aqueousmedium, a mixture initially consisting essentially of sodium fluoride,tetrasodium pyrophosphate, and a water-soluble magnesium salt to form afluorinated disodium magnesium pyrophosphate, and recovering saidfluorinated pyrophosphate, said reactants being employed in theproportions required to form disodium magnesium pyrophosphate containingabout 1% to about 5% by weight of chemically combined fluorine.

10. As a new composition of matter, disodium magnesium pyrophosphatecontaining about 1% to about 5% by weight of chemically combinedfluorine, said composition of matter being produced by the methoddefined in claim 9.

11. The method, which comprises reacting together, in a liquid aqueousmedium, a mixture initially consisting essentially of potassiumfluoride, tetrapotassium pyrophosphate and a water-soluble calcium saltto form a fluorinated dipotassium calcium pyrophosphate, and recoveringsaid fluorinated pyrophosphate, said reactants being employed in theproportions required to form dipotassium calcium pyrophosphatecontaining about 1% to about 5% by weight of chemically combinedfluorine.

12. As a new composition of matter, dipotassium calcium pyrophosphatecontaining about 1% to about 5% by weight of chemically combinedfluorine, said composition of matter being produced by the methoddefined in claim 11.

13. The method, which comprises reacting together,in a liquid aqueousmedium, a mixture initially consisting essentially of potassiumfluoride, tetrapotassium pyrophosphate and a water-soluble magnesiumsalt to form a fluorinated dipotassium magnesium pyrophosphate, andrecovering said fluorinated pyrophosphate, said reactants being employedin the proportions required to form dipotassium magnesium pyrophosphatecontaining about 1% to about 5% by weight of chemically combined fluo-14. As a new composition of matter, dipotassium magnesium pyrophosphatecontaining about 1% to about 5% by weight of chemically combinedfluorine, said composition of matter being produced by the methoddefined in claim 13.

15. The method, which comprises reacting together, in a liquid aqueousmedium, a mixture initially consisting essentially of sodium fluoride,tetrasodium pyrophosphate and a water soluble calcium salt to form afluorinateddisodium calcium pyrophosphate, and recovering saidfluorinated pyrophosphate, said reactants being employed in theproportions required to form disodium calcium pyrophosphate containingabout 2% to about 3.5% by weight of chemically combined fluorine.

16. As a new composition of matter, disodium calcium pyrophosphatecontaining about 2% to about 3.5% by weight of chemically combinedfluorine, said composition of matter being produced by the methoddefined in claim 15.

17. The method, which comprises reacting together, in a liquid aqueousmedium, a mixture initially consisting essentially of sodium fluoride,tetrasodium pyrophosphate and a water-soluble calcium salt to form afluorinated disodium calcium pyrophosphate, and recovering saidfluorinated pyrophosphate, said reactants being employed in theproportions required to form disodium calcium pyrophosphate containingabout 2.9% by weight of chemically combined fluorine.

18. As' a new composition of matter, disodium calcium pyrophosphatecontaining about 2.9% by weight of chemically combined fluorine, saidcomposition of matter being produced by the method defined in claim 17.

19. The method, which comprises reacting together, in a liquid aqueousmedium, a mixture initially consisting essentially of a water solublealkali fluoride, an alkali tetrapyrophosphate and a water solublealkaline earth metal salt to form a fluorinated alkali-alkaline earthmetal pyrophosphate, and recovering said fluorinated pyrophosphate, saidreactants being employed in the amount required to form adialkali-alkaline earth metal pyrophosphate containing about 1% to about5% by weight of chemically combined fluorine and said initial calciumsalt being employed in an amount varying from about 0% to about 200% inexcess of that required to produce said dialkali-alkaline earth metalpyrophosphate.

20. A dentifrice containing about 40% to about 60% by weight of afluorinated dialkali-alkaline earth metal pyrophosphate containing about1% to about 5% by weight of chemically combined fluorine.

21. A tooth powder containing about 90% to about 99% by weight of afluorinated dialkali-alkaline earth metal pyrophosphate containing about1% to about 5% by weight of chemically combined fluorine.

References Cited in the file of this patent UNITED STATES PATENTS1,016,989 Galt Feb. 13, 1912 1,704,218 Rothe Mar. 5, 1929 1,799,882Brenek Apr. 7, 1931 2,266,328 McCullough Dec. 16, 1941 OTHER REFERENCESJournal Amer. Dental Association, volume 38, February 1949, pages204-212, page 210 pertinent.

Mellor: Comprehensive Treatise on Inorganic and Theoretical Chemistry,volume 3, page 892, volume 8, pages 975 and 976, Longman Green Co., NewYork, 1928.

Audrieth and Hill: Recent Developments in the Chemistry of Phosphorus,Journal of Chemical Education, February 1948, pages to 86, page 84 onlycited.

Shourie et al.: Journal Dental Research, August 1950, volume 29, pages529, 533.

Bibby: Journal American Dental Association, volume 34, January 1, 1947,pages 26, 31.

20. A DENTIFRICE CONTAINING ABOUT 40% TO ABOUT 60% BY WEIGHT OF AFLUORINATED DIALKALI-ALKALINE EARTH METAL PYROPHOSPHATE CONTAINING ABOUT1% TO ABOUT 5% BY WEIGHT OF CHEMICALLY COMBINED FLUORINE.